Hierarchically Responsive Alternating Nano-Copolymers with Tailored Interparticle Bonds.

Self-assembly of inorganic nanoparticles (NPs) is an essential tool for constructing structured materials with a wide range of applications. However, achieving ordered assembly structures with externally programmable properties in binary NP systems remains challenging. In this work, we assemble binary inorganic NPs into hierarchically pH-responsive alternating copolymer-like nanostructures in an aqueous medium by engineering the interparticle electrostatic interactions. The polymer-grafted NPs bearing opposite charges are viewed as nanoscale monomers ("nanomers"), and copolymerized into alternating nano-copolymers (ANCPs) driven by the formation of interparticle "bonds" between nanomers. The resulting ANCPs exhibit reversibly responsive "bond" length (i.e., the distance between nanomers) in response to the variation of pH in a range of ~7-10, allowing precise control over the surface plasmon resonance of ANCPs. Moreover, specific interparticle "bonds" can break up at pH≥11, leading to the dis-assembly of ANCPs into molecule-like dimers and trimers. These dimeric and trimeric structures can reassemble to form ANCPs owing to the resuming of interparticle "bonds", when the pH value of the solution changes from 11 to 7. The hierarchically responsive nanostructures may find applications in such as biosensing, optical waveguide, and electronic devices.

Polymer-Tethered Nanoparticles: From Surface Engineering to Directional Self-Assembly.

Current interest in nanoparticle ensembles is motivated by their collective synergetic properties that are distinct from or better than those of individual nanoparticles and their bulk counterparts. These new advanced optical, electronic, magnetic, and catalytic properties can find applications in advanced nanomaterials and functional devices, if control is achieved over nanoparticle organization. Self-assembly offers a cost-efficient approach to produce ensembles of nanoparticles with well-defined and predictable structures. Nanoparticles functionalized with polymer molecules are promising building blocks for self-assembled nanostructures, due to the comparable dimensions of macromolecules and nanoparticles, the ability to synthesize polymers with various compositions, degrees of polymerization, and structures, and the ability of polymers to self-assemble in their own right. Moreover, polymer ligands can endow additional functionalities to nanoparticle assemblies, thus broadening the range of their applications.In this Account, we describe recent progress of our research groups in the development of new strategies for the self-assembly of nanoparticles tethered to macromolecules. At the beginning of our journey, we developed a new approach to patchy nanoparticles and their self-assembly. In a thermodynamically driven strategy, we used poor solvency conditions to induce homopolymer surface segregation in pinned micelles (patches). Patchy nanoparticles underwent self-assembly in a well-defined and controlled manner. Following this work, we overcame the limitation of low yield of the generation of patchy nanoparticles, by using block copolymer ligands. For block copolymer-capped nanoparticles, patch formation and self-assembly were "staged" by using distinct stimuli for each process. We expanded this work to the generation of patchy nanoparticles via dynamic exchange of block copolymer molecules between the nanoparticle surface and micelles in the solution. The scope of our work was further extended to a series of strategies that utilized the change in the configuration of block copolymer ligands during nanoparticle interactions. To this end, we explored the amphiphilicity of block copolymer-tethered nanoparticles and complementary interactions between reactive block copolymer ligands. Both approaches enabled exquisite control over directional and self-limiting self-assembly of complex hierarchical nanostructures. Next, we focused on the self-assembly of chiral nanostructures. To enable this goal, we attached chiral molecules to the surface of nanoparticles and organized these hybrid building blocks in ensembles with excellent chiroptical properties. In summary, our work enables surface engineering of polymer-capped nanoparticles and their controllable and predictable self-assembly. Future research in the field of nanoparticle self-assembly will include the development of effective characterization techniques, the synthesis of new functional polymers, and the development of environmentally responsive self-assembly of polymer-capped nanoparticles for the fabrication of nanomaterials with tailored functionalities.

Identification, expression patterns, evolutionary characteristics and recombinant protein activities analysis of CD209 gene from Megalobrama amblycephala.

CD209 is a type II transmembrane protein in the C-type lectin family, which is involved in the regulation of innate and adaptive immune system. Although it has been widely studied in mammals, but little has been reported about fish CD209 genes. In the present study, Megalobrama amblycephala CD209 (MaCD209) gene was cloned and characterized, its expression patterns, evolutionary characteristics, agglutinative and bacteriostatic activities were analyzed. These results showed that the open reading frame (ORF) of MaCD209 gene was 795 bp, encoding 264 aa, and the calculated molecular weight of the encoded protein was 29.7 kDa. MaCD209 was predicted to contain 2 N-glycosylation sites, 1 functional domain (C-LECT-DC-SIGN-like) and 1 transmembrane domain. Multiple sequence alignment showed that the amino acid sequence of MaCD209 was highly homologous with that of partial fishes, especially the highly conserved C-LECT-DC-SIGN-like domain and functional sites of CD209. Phylogenetic analysis showed that the CD209 genes from M. amblycephala and other cypriniformes fishes were clustered into one group, which was reliable and could be used for evolutionary analysis. Then, adaptive evolutionary analysis of teleost CD209 was conducted, and several positively selected sites were identified using site and branch-site models. Quantitative real-time PCR analysis showed that MaCD209 gene was highly expressed in the liver and heart. Moreover, the expression of MaCD209 was significantly induced upon Aeromonas hydrophila infection, with the peak levels at 4 h or 12 h post infection. The immunohistochemical analysis also revealed increased distribution of MaCD209 protein post bacterial infection. In addition, recombinant MaCD209 (rMaCD209) protein was prepared using a pET32a expression system, which showed excellent bacterial binding and agglutinative activities in a Ca2+-independent manner. However, rMaCD209 could only inhibit the proliferation of Escherichia coli rather than A. hydrophila. In conclusion, this study identified the MaCD209 gene, detected its expression and evolutionary characteristics, and evaluated the biological activities of rMaCD209 protein, which would provide a theoretical basis for understanding the evolution and functions of fish CD209 genes.

Electrostatic Adsorption Behaviors of Charged Polymer-Tethered Nanoparticles on Oppositely Charged Surfaces.

Polymer-grafted hairy nanoparticles (HNPs) that combine the unique properties of inorganic nanoparticles (NPs) and polymers are attractive building blocks for the layer-by-layer assembly of functional hybrid materials, but the adsorption behaviors of HNPs on substrates remain unclear. This article describes a systematic study on the adsorption behaviors of charged polymer-grafted HNPs on oppositely charged substrates in different solvent media via a combination of experiments and simulations. It is shown in simulations that the adsorption process of HNPs is associated with the release of counterions around charged polymers on HNPs, thus resulting in a higher energy barrier of NP adsorption than bare NPs without charged polymer tethers. This energy barrier decreases with decreasing the dielectricity of solvents or ionization degree of grafted polymers or increasing ionic strength of the solution. Furthermore, the theoretical prediction is confirmed in experiments by using a model system of poly(acrylic acid)-grafted silica NPs and poly(diallyldimethylammonium chloride)-modified wafers. The work provides guidance for the electrostatic assembly of HNPs into functional hybrid composites with applications in membranes, optical devices, and biomedicines.

Rapid and sensitive detection of enrofloxacin hydrochloride based on surface enhanced Raman scattering-active flexible membrane assemblies of Ag nanoparticles.

The abuse of antibiotics resulted in the pollution of river is more and more serious and it was necessary to exploit a sensitive detection method to improve the traditional analysis measurement. In this test, it is reported an Ag-based SERS sensing membrane synthesized by the technique of SERS detection and membrane separation. SERS analysis technique presented sensitive detection property, which could be applied into trace analysis. Membrane separation could effectively enrich the analytes to improve the sensitivity. The SERS membrane was synthesized by filtrating Ag nanoparticles (NPs) on the surface and investigating the amount of PVP and Ag NPs to the sensitivity. Meanwhile, the addition of Ag NPs effectively improved the hydrophilia to promote the detection effectivity in the water. By the investigations of optical analysis, the SERS membrane presented high sensitivity in the detection of antibiotics. Under the optimal condition, the SERS intensity presented good linear relationship with the concentration of antibiotics between 1.0 nmol L-1 and 200 nmol L-1. This method provided a sensitive detection approach and broadened the investigation field of antibiotics detection.

Effects of conversion of mangroves into gei wai ponds on accumulation, speciation and risk of heavy metals in intertidal sediments.

Mangroves are often converted into gei wai ponds for aquaculture, but how such conversion affects the accumulation and behavior of heavy metals in sediments is not clear. The present study aims to quantify the concentration and speciation of heavy metals in sediments in different habitats, including gei wai pond, mangrove marsh dominated by Avicennia marina and bare mudflat, in a mangrove nature reserve in South China. The results showed that gei wai pond acidified the sediment and reduced its electronic conductivity and total organic carbon (TOC) when compared to A. marina marsh and mudflat. The concentrations of Cd, Cu, Zn and Pb at all sediment depths in gei wai pond were lower than the other habitats, indicating gei wai pond reduced the fertility and the ability to retain heavy metals in sediment. Gei wai pond sediment also had a lower heavy metal pollution problem according to multiple evaluation methods, including potential ecological risk coefficient, potential ecological risk index, geo-accumulation index, mean PEL quotients, pollution load index, mean ERM quotients and total toxic unit. Heavy metal speciation analysis showed that gei wai pond increased the transfer of the immobilized fraction of Cd and Cr to the mobilized one. According to the acid-volatile sulfide (AVS) and simultaneously extracted metals (SEM) analysis, the conversion of mangroves into gei wai pond reduced values of ([SEM] - [AVS])/foc, and the role of TOC in alleviating heavy metal toxicity in sediment. This study demonstrated the conversion of mangrove marsh into gei wai pond not only reduced the ecological purification capacity on heavy metal contamination, but also enhanced the transfer of heavy metals from gei wai pond sediment to nearby habitats.

Interactive effects of single, binary and trinary trace metals (lead, zinc and copper) on the physiological responses of Kandelia obovata seedlings.

Heavy metals are considered important environmental contaminants, and their mixture toxicity on plants has complex mutual interactions. The interactive effects of heavy metals on growth, photosynthetic parameters, lipid peroxidation and compatible osmolytes were studied in Kandelia obovata grown for 5 months in sediment treated with combinations of lead (Pb), zinc (Zn) and copper (Cu). The results showed no significant reduction of biomass under heavy metal stresses, except for decreased root biomass under higher Pb + Cu treatment, indicating high tolerance of K. obovata to heavy metal stress. Only the photosynthetic parameters, including net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr), decreased with increasing concentration of treatments (except for Pb + Cu and Pb + Zn + Cu). Trinary treatment (Pb + Zn + Cu) increased biomass and the photosynthetic parameters when compared to the external addition of binary metals. In the roots, biomass and soluble sugar content were lower under binary than trinary treatments, indicating that the combination of Zn and Cu exhibited improved effects of alleviating toxicity than each of them alone in Pb-containing combined treatments. In the leaves, Zn-containing combined treatments significantly decreased malondialdehyde (MDA), soluble sugar and proline content in low concentration, while Pb + Cu treatments significantly increased these parameters (P < 0.05). The correlation analysis showed that leaf MDA and proline content were negatively correlated with Zn concentration (P < 0.05). Zn could alleviate the effects of combined heavy metal stress, and Pb + Cu treatment showed synergistic effects in leaves. The positive correlations between MDA content and the osmotic parameters showed that osmotic stress and lipid membranes oxidation exist simultaneously under multiple heavy metal stresses. Therefore, biomass, Tr, leaf MDA, leaf proline content and soluble sugar content could indicate metal mixture toxicity to mangrove seedlings.

Does ammonium nitrogen affect accumulation, subcellular distribution and chemical forms of cadmium in Kandelia obovata?

Heavy metals and nutrients are commonly found in mangrove sediments, but the effect of nutrients on heavy metals in mangrove plants is not clear. A study quantifying the effects of ammonium nitrogen (NH4+-N) on the accumulation, subcellular distribution and chemical forms of cadmium (Cd) in Kandelia obovata seedlings were conducted. The experiment consisted of four levels of NH4+-N (0, 10, 50 and 100 mg L-1) in each of which consisted of four Cd levels (0, 1, 5 and 10 mg L-1). The results showed that NH4+-N magnified the Cd toxicity due to reduced plant biomass, especially with 10 mg L-1 Cd and 100 mg L-1 NH4+-N supply. NH4+-N, especially at 100 mg L-1, enhanced the concentration and accumulation of Cd in root but its role on Cd translocation from root to stem and leaf was limited, probably due to low translocation factor. At subcellular level, Cd mainly accumulated in root cell wall but its fractionation depended on Cd levels. Under the stress of 1 and 5 mg L-1 Cd, 50 mg L-1 NH4+-N supply improved transfer of Cd from root cell wall into cell, and increased pectate and protein integrated forms of intracellular Cd to alleviate Cd toxicity. Under the stress of 10 mg L-1 Cd, NH4+-N supply promoted the deposition of Cd on root cell wall to restrain its transfer to root cell, which was verified by the reduced levels of pectate and protein integrated forms of Cd in root cell. Thus, NH4+-N supply improved immobilization of Cd in roots and alleviated Cd toxicity through integration with pectate and protein as well as cell wall combinations in root of K. obovata.

Advanced Glycation End Products Impair Ca2+ Mobilization and Sensitization in Colonic Smooth Muscle Cells via the CAMP/PKA Pathway.

BACKGROUND/AIMS: Excessive production of advanced glycation end products (AGEs) has been implicated in diabetes-related complications. This study aimed to investigate the mechanism by which AGEs potentially contribute to diabetes-associated colonic dysmotility. METHODS: Control and streptozotocin (STZ)-induced diabetic groups were treated with aminoguanidine (AG). The colonic transit time and contractility of circular muscle strips was measured. ELISA, immunohistochemistry and western blotting were used to measure Nε-carboxymethyl-lysine (CML) levels. Primary cultured colonic smooth muscle cells (SMCs) were used in complementary in vitro studies. RESULTS: Diabetic rats showed prolonged colonic transit time, weak contractility of colonic smooth muscle strips, and elevated levels of AGEs in the serum and colon tissues. cAMP levels, protein kinase-A (PKA) activities, and inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) phosphorylation were increased in the colon muscle tissues of diabetic rats, whereas RhoA/Rho kinase activity and myosin phosphatase target subunit 1 (MYPT1) phosphorylation were reduced. The inhibition of the production of AGEs (AG treatment) reduced these effects. In cultured colonic SMCs, AGE-BSA treatment increased IP3R3 phosphorylation and reduced intracellular Ca2+ concentration, myosin light chain (MLC) phosphorylation, RhoA/Rho kinase activity, and MYPT1 phosphorylation. The PKA inhibitor H-89 and anti-RAGE antibody inhibited the AGE-BSA-induced impairment of Ca2+ signaling and cAMP/PKA activation. CONCLUSION: AGEs/RAGE participate in diabetes-associated colonic dysmotility by interfering with Ca2+ signaling in colonic SMCs through targeting IP3R3-mediated Ca2+ mobilization and RhoA/Rho kinase-mediated Ca2+ sensitization via the cAMP/PKA pathway.

Engineering the Electrostatic Interactions between Oppositely Charged Polymer-Grafted Nanoparticles for Constructing Colloid Molecules on Substrates.

Arrays of nanoparticle (NP) clusters with controlled architectures show broad applications in nanolasers, sensors, and photocatalysis, but the fabrication of these arrays on substrates remains a grand challenge. This review presents a highly effective polymer-based strategy for the process-directed self-assembly of binary polyelectrolyte-grafted NPs (PGNPs) bearing opposite charges into stable colloidal molecules (CMs) on substrates via electrostatic interactions. The coordination number (x) of ABx CMs can be tuned by adjusting the pH or ionic strength of the solution or by employing different combinations of PGNPs with varying charge densities. Large-area CMs with diverse structures ranging from AB to AB7 can be constructed on substrates in high yields. This approach is applicable to PGNPs with different cores of NPs. This assembly strategy offers a useful tool for the fabrication of structurally precise assemblies on substrates with broad applications.

Effects of total gonadotropin dose on embryo quality and clinical outcomes with AMH stratification in IVF cycles: a retrospective analysis of 12,588 patients.

BACKGROUND: Recent studies about the effect of gonadotropin (Gn) dose on the clinical outcomes of IVF are still controversial, and no studies have analyzed the relationship between Gn dose and embryo quality. Since AMH is a strong predictor of oocyte quality, we aim to evaluate the relationship between total Gn dose and embryo quality and clinical outcomes at different AMH levels in IVF cycles. METHODS: A total of 12,588 patients were enrolled in the retrospective study. The included cycles were categorized by serum AMH levels (AMH ≤ 1 ng/ml, 1 ng/ml < AMH ≤ 3 ng/ml, 3 ng/ml < AMH ≤ 5 ng/ml, AMH > 5 ng/ml), total Gn dosage (< 1875 IU, 1875-3750 IU and ≥ 3750 IU) and female age (< 35 years and 35-42 years). The embryo quality and clinical outcomes were the measure outcomes. RESULTS: The top-day3 embryos rate decreased with the increase of total Gn dose in nearly all age and AMH subgroups, but this trend was not obvious in the AMH > 5 ng/ml group and AMH ≤ 1 ng/ml group. The blastocyst formation rate and high-quality blastulation rate had a negative relationship with Gn does for women aged < 35 years in the AMH ≤ 5 ng/ml groups, except for the AMH > 5 ng/ml group (P < 0.001). However, when women were 35-42 years old, regardless of AMH levels, the blastocyst formation rate and high-quality blastulation rate decreased as Gn dose increased. Clinical outcomes (implantation rate, clinical pregnancy rate and live birth rate) decreased with the increase of Gn dose in all ages and AMH stratifications. CONCLUSIONS: The total dose of Gn may have different effects on embryo quality at different serum AMH levels, and the negative effects of total dose of Gn on clinical outcomes may be realized by impairing both embryo quality and endometrium.

Multiple heavy metals affect root response, iron plaque formation, and metal bioaccumulation of Kandelia obovata.

Multiple heavy metal pollution in mangrove wetlands is serious. Kandelia obovata seedlings were cultured in pots in which lead (Pb), zinc (Zn) and copper (Cu) were added separately and in combinations. The results showed that heavy metal stress improved the rate of root oxygen leakage, enhanced root activity, and reduced root porosity. The root under single heavy metal stress was impacted by the addition of other heavy metals, demonstrating antagonistic or synergistic effects. Iron plaque (IP) formation was improved under single Zn or Cu stress, and inhibited in binary stress of Pb + Cu. The adsorptions of IP on heavy metals in combined stress (Pb, 62-116 µg g-1; Zn, 194-207 µg g-1; Cu, 35-52 µg g-1) were higher than that in single stress (Pb, 18 µg g-1; Zn, 163 µg g-1; Cu, 22 µg g-1). K. obovata accumulated higher levels of heavy metals in root (Pb, 7-200 µg g-1; Cu, 4-78 µg g-1), compared with IP (Pb, 18-116 µg g-1; Cu, 22-52 µg g-1), stem (Pb, 3-7 µg g-1; Cu, 9-17 µg g-1), and leaf (Pb, 2-4 µg g-1; Cu, 4-7 µg g-1). Correlation analysis showed that single and binary stresses affected K. obovata, with more significant effect of trinary stress. Regression path analysis showed that multiple heavy metal stress firstly affected root, then indirectly contributed to IP formation, as well as heavy metal in IP and root; at last, heavy metal in IP directly contributed to heavy metal bioaccumulations in root.

Potential biomarkers for clinical outcomes of IVF cycles in women with/without PCOS: Searching with metabolomics.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinological and metabolic disorder which is the common cause of female infertility. The dysmetabolism displayed in it has not been completely ascertained. Metabonomics may shed light on understanding many small molecule endogenous metabolites and their associated metabolic pathways. Objective: To analyze the different metabolites and related metabolic pathways in follicular fluid and embryo culture fluid of PCOS and non-PCOS groups. Finding markers predictable for clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) treatment. Population and sample: 60 women who underwent IVF-ET were selected, including 30 with PCOS and 30 with the fallopian tubal issues only. We collected the first tube follicular fluid (FF) of all patients at the time of oocyte pick up and the waste embryo culture medium (ECM) after D3 high-quality embryo transplant. Methods: All samples were performed nontargeted Ultra High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-QE-MS) analysis. Related metabolic pathways were screened by KEGG annotation. To search potential indicators, the logistic regression was made combined with clinical data. Mean outcome measures: Predictive performance of markers of clinical outcomes (pregnancy rate, delivery rate, live birth rate, miscarriage rate) of assisted reproductive technology (ART). Results: Comparing the PCOS group against the non-PCOS group, we found 11 significantly different metabolites in the FF and 56 in the ECM. There are a total of 11 kinds of biomarkers associated with clinical outcomes. Androsterone sulfate, Glycerophosphocholine, and Elaidic carnitine seem robust to predict the abortion rate of the PCOS group, with an AUC of 0.941, 0.933, 0.933, respectively. The glycerol phospholipid metabolic pathway is enriched in both the follicular fluid and embryo culture fluid. Conclusions: The differential metabolites were mainly a variety of lipids. Some of them can predict clinical outcomes to a certain extent.

Effect of visfatin on KATP channel upregulation in colonic smooth muscle cells in diabetic colon dysmotility.

The mechanisms of diabetes-related gastrointestinal dysmotility remains unclear. This study aimed to investigate the effect and mechanisms of proinflammatory adipokine visfatin (VF) in the contractile dysfunction of diabetic rat colonic smooth muscle. Twenty Sprague-Dawley rats were randomly divided into control and type 2 diabetes mellitus groups. VF levels in the serum and colonic muscle tissues were tested, the time of the bead ejection and contractility of colonic smooth muscle strips were measured, and the expression of ATP-sensitive potassium (KATP) channels in the colonic muscle tissues was analyzed. In vitro, we tested VF's effects on intracellular reactive oxygen species (ROS) levels, NF-κB's nuclear transcription, KATP channel expression, intracellular Ca2+ concentrations, and myosin light chain (MLC) phosphorylation in colonic smooth muscle cells (CSMCs). The effects of NAC (ROS inhibitor) and BAY 11-7082 (NF-κB inhibitor) on KATP expression were also tested. Diabetic rats showed elevated VF levels in serum and colonic muscle tissues, a delayed distal colon ejection response time, weakened contractility of colonic smooth muscle strips, and increased KATP channel expression in colonic muscle tissues. VF significantly inhibited the contractility of colonic smooth muscle strips from normal rats. In cultured CSMCs, VF caused ROS overload, increased NF-κB nuclear transcription activity and increased expression of Kir6.1, eventually reducing intracellular Ca2+ levels and MLC phosphorylation. NAC and BAY 11-7082 inhibited the VF-induced Kir6.1 upregulation. In conclusion, VF may cause contractile dysfunction of CSMCs by upregulating the expression of the Kir6.1 subunit of KATP channels via the ROS/NF-κB pathway and interfering with Ca2+ signaling.

Centimeter-Scale Superlattices of Three-Dimensionally Orientated Plasmonic Dimers with Highly Tunable Collective Properties.

The precise organization and orientation of plasmonic molecules on substrates is crucial to their application in functional devices but still remains a grand challenge. This article describes a bottom-up strategy to efficiently fabricate centimeter-scale superlattices of three-dimensionally oriented plasmonic dimers with highly tunable collective optical properties on substrates. The in-plane (i.e., X-Y plane) and out-of-plane (i.e., along Z-axis) orientation of the constituent plasmonic dimers can be precisely controlled by a combination of directional capillary force and supporting polymer film. Our experimental measurements and numerical simulations show that the macroscopic dimer superlattices exhibit polarization-dependent plasmon Fano resonances in air and multimodal surface lattice resonances with high quality factors in a homogeneous medium, owing to the high positional and orientational ordering of the subunits. Our strategy enables the fabrication of complex plasmonic nanostructures with precise configurations for advanced plasmonic devices such as plasmon nanolasing and metamaterials.

Bioaccessibility-corrected health risk of heavy metal exposure via shellfish consumption in coastal region of China.

A systematic investigation into bioaccessible heavy metals in shellfish Crassostrea ariakensis, Chlamys farreri, and Sinonovacula constricta from coastal cities Shenzhen, Zhoushan, Qingdao, and Dandong was carried out to assess the potential health risk to residents in coastal regions in China. The bioaccessible fractions of heavy metals were (µg‧g-1): Zn (0.63-15.01), Cu (0.10-12.91), Cd (0.01-0.64), As (0.11-0.33), Cr (0.07-0.12), Pb (0.01-0.03). The bioaccessibilities of heavy metals were Cr 61.86%, inorganic As (iAs) 60.44%, Pb 55.74%, Cu 46.83%, Zn 28.16%, and Cd 24.99%. As for child and adult, the bioaccessibility-corrected estimated daily intakes were acceptable and the non-carcinogenic risks posed by heavy metals were not obvious. The carcinogenic risks posed by bioaccessible heavy metals at the fifth percentile were 10-fold higher than the acceptable level (10-4), with iAs and Cd to be the major contributors, regardless of child or adult. The probabilistic estimation showed the low risk of shellfish consumption, which was verified by higher values of maximum allowable consumption rate and monthly meals at the 95 percentile; while some control of consumption rate and monthly meals was necessary for reducing heavy metal exposure of most shellfish samples, except for the safe consumption of S. constricta for both child and adult in Qingdao and Shenzhen, China.

The Development of Nomograms to Predict Blastulation Rate Following Cycles of In Vitro Fertilization in Patients With Tubal Factor Infertility, Polycystic Ovary Syndrome, or Endometriosis.

It is well known that the transfer of embryos at the blastocyst stage is superior to the transfer of embryos at the cleavage stage in many respects. However, the rate of blastocyst formation remains low in clinical practice. To reduce the possibility of wasting embryos and to accurately predict the possibility of blastocyst formation, we constructed a nomogram based on range of clinical characteristics to predict blastocyst formation rates in patients with different types of infertility. We divided patients into three groups based on female etiology: a tubal factor group, a polycystic ovary syndrome group, and an endometriosis group. Multiple logistic regression was used to analyze the relationship between patient characteristics and blastocyst formation. Each group of patients was divided into a training set and a validation set. The training set was used to construct the nomogram, while the validation set was used to test the performance of the model by using discrimination and calibration. The area under the curve (AUC) for the three groups indicated that the models performed fairly and that calibration was acceptable in each model.

Alteration of sphingosine-1-phosphate with aging induces contractile dysfunction of colonic smooth muscle cells via Ca2+ -activated K+ channel (BKCa ) upregulation.

BACKGROUND: Age-associated changes alter calcium-activated potassium channel (BKCa ) expression of colon. Sphingolipids (SLs) are important cell membrane structural components; altered composition of SLs may affect BKCa expression. This study investigated the mechanism by which sphingosine-1-phosphate (S1P) contributes to age-associated contractile dysfunction. METHODS: Fifty male Sprague Dawley rats of different ages were randomly assigned to five age-groups, namely 3, 6, 12, 18, and 24 months. BKCa expression, S1P levels, and phosphorylated myosin light chain (p-MLC) levels were tested in colonic tissues. In the absence and presence of S1P treatment, BKCa expression, p-MLC levels, and intracellular calcium mobilization were tested in vitro. BKCa small interfering RNA (siRNA) was used to investigate whether p-MLC expression and calcium mobilization were affected by BKCa in colonic smooth muscle cells (SMCs). The expressions of phosphorylated protein kinase B, c-Jun N-terminal kinases (JNKs), extracellular-regulated protein kinases, nuclear factor kappa-B (NF-κB), and protein kinase Cζ (PKCζ ) were examined to investigate the correlation between S1P and BKCa . KEY RESULTS: Sphingosine-1-phosphate levels and sphingosine-1-phosphate receptor 2 (S1PR2) and BKCa expressions were upregulated and p-MLC expression was downregulated in the colonic tissues, age dependently. In the cultured SMCs, S1P treatment increased BKCa expression and reduced calcium concentration and p-MLC was observed. BKCa siRNA increased calcium concentration, and p-MLC levels significantly compared with control. We also showed that S1P upregulated BKCa through PKCζ , JNK, and NF-κB pathways. CONCLUSIONS AND INFERENCES: In conclusion, S1P and S1PR2 participate in age-associated contractile dysfunction via BKCa upregulation through PKCζ , JNK, and NF-κB pathways.

miR-153 enhances the therapeutic effect of radiotherapy by targeting JAG1 in pancreatic cancer cells.

Pancreatic cancer is one of the deadliest diseases, due to the lack of early symptoms and resistance to current therapies, including radiotherapy. However, the mechanisms of radioresistance in pancreatic cancer remain unknown. The present study explored the role of microRNA-153 (miR-153) in radioresistance of pancreatic cancer. It was observed that miR-153 was downregulated in pancreatic cancer and positively correlated with patient survival time. Using stably-infected pancreatic cancer cells that overexpressed miR-153 or miR-153 inhibitor, it was found that miR-153 overexpression sensitized pancreatic cancer cells to radiotherapy by inducing increased cell death and decreased colony formation, while cells transfected with the miR-153 inhibitor promoted radioresistance. Further investigation demonstrated that miR-153 promoted radiosensitivity by directly targeting jagged canonical Notch ligand 1 (JAG1). The addition of recombinant JAG1 protein in the cell cultures reversed the therapeutic effect of miR-153. The present study revealed a novel mechanism of radioresistance in pancreatic cancer and indicated that miR-153 may serve as a potential therapeutic target for radioresistance.

MicroRNA-155 promotes apoptosis of colonic smooth muscle cells and aggravates colonic dysmotility by targeting IGF-1.

Colonic dysmotility as a complication of diabetes affects public health; however, the underlying molecular mechanisms have remained elusive. Insulin-like growth factor-1 (IGF-1) was previously demonstrated to prevent apoptosis of colonic smooth muscle cells (SMCs) and alleviate colonic dysmotility in diabetic rats. However, the regulatory mechanisms upstream of IGF-1 in colonic dysmotility have remained to be determined. The present study reports on microRNA-155 (miR-155), initially identified using bioinformatics, as a direct upstream regulator of IGF-1. In colonic SMCs, miR-155 negatively regulated IGF-1 expression at the post-transcriptional level, as identified through ectopic overexpression and knockdown experiments. A luciferase reporter assay further demonstrated that miR-155 inhibits IGF-1 through binding to its 3'-untranslated region. Furthermore, overexpression of miR-155 led to increased apoptosis of colonic SMCs and a decrease in the thickness of colonic smooth muscle tissues of diabetic mice, indicating miR-155 aggravates colonic dysmotility. By contrast, knockdown of miR-155 induced the opposite effect. Overall, the results of the present study suggest a role of miR-155 in colonic dysmotility, thereby providing a novel therapeutic target.